ADC Therapeutics SA

Previous wording

Following the publication of topline results from the LOTIS-5, we discussed the results with the FDA. The FDA noted that the increased Grade 5 adverse events in the treatment arm, compared to the control arm, when assessed in the context of a marginal treatment benefit, processes, substantial concerns that the trial results are not supportive of a favorable benefit-risk assessment or verification of clinical benefit. In the event we decide not to submit an sBLA for LOTIS 5 (or a similar supplemental application in foreign jurisdictions) or in the event we submit an sBLA to the FDA for LOTIS-5 (or a similar supplemental application in foreign jurisdictions), the FDA and other regulatory authorities may determine that the data is insufficient for approval in earlier lines of therapy or for full approval in third-line or later setting. As a result, an additional confirmatory trial may be required, which will require significant time and resources and be subject to the same risks as other clinical trials and the timing and results of which are uncertain. While we are currently able to continue to commercialize ZYNLONTA in the third line or later setting under its existing accelerated approval in the United States (and our partners in other jurisdiction are able to commercialize under similar conditional approvals), continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The LOTIS-5 trial results could lead regulatory authorities to seek withdrawal of current approvals for ZYNLONTA as a monotherapy in 3L+DLBCL. Further, the results of the LOTIS-5 trial and the perception of the benefit-risk profile of the drug could adversely affect sales of the product and affect enrollment and participation in and perception of our other clinical trials involving ZYNLONTA for other indications and likelihood of approval or compendia inclusion for other indications.

Current wording

Following the publication of topline results from the LOTIS-5, we discussed the results with the FDA. The FDA noted that the increased Grade 5 adverse events in the treatment arm, compared to the control arm, when assessed in the context of a marginal treatment benefit, poses, substantial concerns that the trial results are not supportive of a favorable benefit-risk assessment or verification of clinical benefit. In the event we decide not to submit an sBLA for LOTIS 5 (or a similar supplemental application in foreign jurisdictions) or in the event we submit an sBLA to the FDA for LOTIS-5 (or a similar supplemental application in foreign jurisdictions), the FDA and other regulatory authorities may determine that the data is insufficient for approval in earlier lines of therapy or for full approval in third-line or later setting. As a result, an additional confirmatory trial may be required, which will require significant time and resources and be subject to the same risks as other clinical trials and the timing and results of which are uncertain. While we are currently able to continue to commercialize ZYNLONTA in the third line or later setting under its existing accelerated approval in the United States (and our partners in other jurisdiction are able to commercialize under similar conditional approvals), continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The LOTIS-5 trial results could lead regulatory authorities to seek withdrawal of current approvals for ZYNLONTA as a monotherapy in 3L+DLBCL. Further, the results of the LOTIS-5 trial and the perception of the benefit-risk profile of the drug could adversely affect sales of the product and affect enrollment and participation in and perception of our other clinical trials involving ZYNLONTA for other indications and likelihood of approval or compendia inclusion for other indications.